Over the past few years, research on non-acidic substances with an anti-inflammatory activity have increased. Of these, a few derivatives related structurally to the glucides have proved to be particularly interesting.
They normally exert a venotropic action and inhibit the effects of antigen-antibody reaction. A stimulating action on fibrinolytic activity has also been observed both in vitro and in vivo. A compound in this class which has been studied in some detail is tribenoside or ethyl-3,5,6-tri-O-benzyl-D-glucofuranoside (Glyvenol).
Interest in this class of compounds is not only associated with effective therapeutic activity but also with their innocuity at a gastric and general level. It is known that steroid and non-steroid anti-inflammatory agents give rise to very considerable side effects and, because of this, their use must often be discontinued or suspended or the dose reduced, thus seriously prejudicing the final therapeutic result. Phenylbutazone, acetylsalicylates and cortisones give rise to ulcerogenic effects of different intensity, even causing haemorrhagic manifestations which can be fatal; non-steroid anti-inflammatory agents can produce hepatotoxic manifestations, involving an immunitary mechanism of hypersensibilisation, with icteric-type manifestations or fatty degeneration. Some non-steroid anti-inflammatory agents, such as phenylbutazone, have been described as being nephrotoxic and they can give rise to neuropsychic disturbances and either sensory symptoms or allergic reactions at a cutaneous and staminal cell level.
Therefore, interest in atoxic anti-inflammatory agents is more than justified, bearing in mind that anti-inflammatory therapy is generally carried out on a medium or long-term basis.
Of the derivatives structurally related to the glucides, the best known is the above-mentioned ethyl 3,5,6-tri-O-benzyl-D-glucofuranoside (Glyvenol): ##STR1## This is a compound with anti-inflammatory and anti-allergic activity which is used in the treatment of venous disorders in order to reduce the permeability of blood vessel walls and to inhibit exudative processes.
Considering the novelty of its structure, we have investigated whether a pharmacological activity can even be found in similar but novel compounds.
Beginning, therefore, with D-glucose, we have prepared 1,2:5,6-di-O-isopropylidene-.alpha.-D-glucofuranose (II): ##STR2## as well as 1,2-O-isopropylidene-.alpha.-D-glucofuranose and 1,2-O-isopropylidene-3,5,6-tri-O-benzyl-.alpha.-D-glucofuranose (1; Glen W. L., Myers G. S., Grant G. A., J. Chem. Soc., 2568/1951; (2) Meyer A. S., Reichstein T., Helv. Chim. Acta, 29, 139/1946; (3) Huber G., Rossi A., Helv. Chim. Acta, 51, 1185/1968) and have compared these compounds with (I) for anti-inflammatory activity against carrageenin-induced oedema (500 mg/kg, p.o. in rats).
Preliminary tests showed, surprisingly, that (II) has an activity which is fully comparable with that of (I). Therefore, we have prepared a number of 3-O-derivatives in order to obtain even more potent compounds.